Genetic polymorphism of IL-23R influences susceptibility to HCV-related hepatocellular carcinoma

Labib, Hany A.; Ahmed, Hanan Samir; Shalaby, Sally M.; Wahab, Essam A; Hamed, Emad F

doi:10.1016/j.cellimm.2015.01.012

Cited by 13 publications

(6 citation statements)

References 34 publications

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“…Patients carrying low-production haplotypes of IL-10 and TNF-a 308 GG genotype have a higher risk of developing HCC [149]. Moreover, a rare variant of IL-23R was observed to correlate with reduced risk of HCV-related HCC in Egyptian patients [150]. Also, a HCC-associated polymorphism was found in the VEGF gene, which correlates with higher VEGF expression levels [122].…”

Section: Role Of Host and Virus Genetic Factors In Hcv-related Hccmentioning

confidence: 98%

Molecular mechanisms of hepatitis C virus–induced hepatocellular carcinoma

Vescovo

Refolo

Vitagliano

et al. 2016

Clinical Microbiology and Infection

123

119

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Hepatitis C virus (HCV) is a major leading cause of hepatocellular carcinoma (HCC). HCV-induced hepatocarcinogenesis is a multistep process resulting from a combination of pathway alterations that are either caused directly by viral factors or immune mediated as a consequence of a chronic state of inflammation. Host genetic variation is now emerging as an additional element that contribute to increase the risk of developing HCC. The advent of direct-acting antiviral agents foresees a rapid decline of HCC rate in HCV patients. However, a full understanding of the HCV-mediated tumourigenic process is required to elucidate if pro-oncogenic signatures may persist after virus clearance, and to identify novel tools for HCC prevention and therapy. In this review, we summarize the current knowledge of the molecular mechanisms responsible for HCV-induced hepatocarcinogenesis.

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Section: Role Of Host and Virus Genetic Factors In Hcv-related Hccmentioning

confidence: 98%

Molecular mechanisms of hepatitis C virus–induced hepatocellular carcinoma

Vescovo

Refolo

Vitagliano

et al. 2016

Clinical Microbiology and Infection

123

119

View full text Add to dashboard Cite

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“…About 27% of cases of cirrhosis and 25% of hepatocellular carcinoma (HCC) worldwide are secondary to HCV infection[2]. Multiple genetic factors identified within the past few years have been shown to be associated with the predisposition to chronic liver disease and the progression to cirrhosis and HCC[3,4]. The single nucleotide polymorphism (SNP) rs738409 C>G (isoleucine to methionine substitution at position 148, I148M) in the PNPLA3 gene has been strongly linked to progression of liver disease in multiple studies, and this association was confirmed in meta-analyses of the spectrum of alcoholic liver disease (ALD)[5] as well as non-alcoholic fatty liver disease (NAFLD)[6-9].…”

Section: Introductionmentioning

confidence: 99%

PNPLA3polymorphism increases risk for and severity of chronic hepatitis C liver disease

Salameh

Masadeh

Hanayneh³

et al. 2016

WJH

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AIMTo examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum.METHODSLiterature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms.RESULTSOf 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity.CONCLUSIONPNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients.

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“…Host genetic factors in several cytokines and cytokine receptors, including polymorphisms in TNF-α , IL-10 , IL-23R , TLR4 , and VEGF , also contribute to HCC risk [ 175 , 176 ]. Patients with haplotypes associated with reduced production of TNF-α and IL-10 are at higher risk of HCC [ 177 ], whereas patients with a rare variant in IL-23R have lower risk of HCC [ 178 ]. Based on a retrospective study of patients treated for HCV infection in Taiwan, a polymorphism in IFNL3 (formerly known as IL28B ) was found to be an independent risk factor for development of HCC following treatment.…”

Section: Molecular Mechanisms Of Hccmentioning

confidence: 99%

Molecular Mechanisms of Hepatocarcinogenesis Following Sustained Virological Response in Patients with Chronic Hepatitis C Virus Infection

Hayes

Zhang

et al. 2018

Viruses

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Despite the success of direct-acting antiviral (DAA) agents in treating chronic hepatitis C virus (HCV) infection, the number of cases of HCV-related hepatocellular carcinoma (HCC) is expected to increase over the next five years. HCC develops over the span of decades and is closely associated with fibrosis stage. HCV both directly and indirectly establishes a pro-inflammatory environment favorable for viral replication. Repeated cycles of cell death and regeneration lead to genomic instability and loss of cell cycle control. DAA therapy offers >90% sustained virological response (SVR) rates with fewer side effects and restrictions than interferon. While elimination of HCV helps to restore liver function and reverse mild fibrosis, post-SVR patients remain at elevated risk of HCC. A series of studies reporting higher than expected rates of HCC development among DAA-treated patients ignited debate over whether use of DAAs elevates HCC risk compared to interferon. However, recent prospective and retrospective studies based on larger patient cohorts have found no significant difference in risk between DAA and interferon therapy once other factors are taken into account. Although many mechanisms and pathways involved in hepatocarcinogenesis have been elucidated, our understanding of drivers specific to post-SVR hepatocarcinogenesis is still limited, and lack of suitable in vivo and in vitro experimental systems has hampered efforts to examine etiology-specific mechanisms that might serve to answer this question more thoroughly. Further research is needed to identify risk factors and biomarkers for post-SVR HCC and to develop targeted therapies based on more complete understanding of the molecules and pathways implicated in hepatocarcinogenesis.

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Genetic polymorphism of IL-23R influences susceptibility to HCV-related hepatocellular carcinoma

Cited by 13 publications

References 34 publications

Molecular mechanisms of hepatitis C virus–induced hepatocellular carcinoma

Molecular mechanisms of hepatitis C virus–induced hepatocellular carcinoma

PNPLA3polymorphism increases risk for and severity of chronic hepatitis C liver disease

Molecular Mechanisms of Hepatocarcinogenesis Following Sustained Virological Response in Patients with Chronic Hepatitis C Virus Infection

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